CompletedNCT02581787Updated Mar 27, 2024Results posted

SABR-ATAC: A Trial of TGF-beta Inhibition and Stereotactic Ablative Radiotherapy for Early Stage Non-small Cell Lung Cancer

A Phase 1/2 interventional study of Fresolimumab and Stereotactic Body Radiation Therapy in Stage IA Non-Small Cell Lung Carcinoma and Stage IB Non-Small Cell Lung Carcinoma, sponsored by Maximilian Diehn. Completed at 1 site in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2024-03-27.

Sponsored by Maximilian Diehn · Phase 1/2, Interventional, and Treatment

Phase: Phase 1/2
Study type: Interventional
Enrollment: 28
Allocation: Non-randomized
Ages: 18 Years and older
Sex: All

Study summary

The SABR-ATAC trial (Stereotactic Ablative Radiotherapy and anti-TGFB Antibody Combination) is a phase I/II trial that studies the side effects and efficacy of fresolimumab, an anti-transforming growth factor beta (TGFB) antibody, when given with stereotactic ablative radiotherapy in patients with stage IA-IB non-small cell lung cancer. Fresolimumab may inhibit radiation side effects and block tumor growth through multiple mechanisms. Stereotactic ablative radiotherapy (SABR), also known as stereotactic body radiotherapy (SBRT), is a specialized form of radiation therapy that precisely delivers high dose radiation directly to tumors, thus killing tumor cells and minimizing damage to normal tissue. Giving fresolimumab with SABR may work better in treating patients with early stage non-small cell lung cancer than treating with SABR alone.

Read the detailed description

PRIMARY OBJECTIVES:

Phase 1: Evaluate the safe dose of fresolimumab in combination with stereotactic ablative radiotherapy (SABR) in patients.

Phase 2. Evaluate the rate of radiation induced pulmonary fibrosis after SABR plus fresolimumab.

SECONDARY OBJECTIVES:

I. Evaluate potential adverse events in patients receiving fresolimumab plus SABR. (Phase I) II. Evaluate post treatment changes in pulmonary function. (Phase I) III. Evaluate recurrence rates and progression free survival. (Phase I) IV. Assess pharmacokinetics (PK) of fresolimumab in combination with SABR (optional for patient). (Phase I) V. Evaluate the rate and severity of radiation induced pulmonary fibrosis after SABR plus fresolimumab. (Phase I) VI. Evaluate the severity of radiation induced pulmonary fibrosis after SABR plus fresolimumab. (Phase II) VII. Evaluate potential adverse events in patients receiving fresolimumab plus SABR. (Phase II) VIII. Evaluate post treatment changes in pulmonary function. (Phase II) IX. Evaluate recurrence rates and progression free survival. (Phase II)

OUTLINE: This is a phase I, dose escalation study of fresolimumab followed by a phase II study.

Phase 1: A cohort of 5 patients receive the pre-selected dose of 3mg/kg of fresolimumab. If one patient experiences a DLT, an additional 5 patients will be enrolled at 3 mg/kg. If no more patients experience a DLT, then 3 mg/kg will be the dose for the Phase 2 component. If 2 or more patients experience a DLT in the total expanded cohort (or 2 or more patients in the initial cohort experience DLT), then the investigational dose of fresolimumab will be changed to 1 mg/kg. If 2 or more patients in the initial cohort experience DLT before all 5 patients have been enrolled, the remaining patients will receive the lower dose of 1 mg/kg.
Phase 2: Patients receive fresolimumab intravenously (IV) on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.

After completion of study treatment, patients are followed up at 3, 6, and 12 months.

Conditions studied

Stage IA Non-Small Cell Lung Carcinoma
Stage IB Non-Small Cell Lung Carcinoma

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In context

Carcinoma

6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.

This study's enrollment of 28 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.

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Lead sponsor

This is the only study on the registry with Maximilian Diehn as lead sponsor.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Inclusion criteria

Newly diagnosed, histologically proven (or strongly suspected, see below) T1-T2aN0M0 (Stage IA-IB) non-small cell lung cancer (NSCLC), with maximum tumor diameter =\< 5 cm under consideration for stereotactic ablative body radiotherapy (SABR) as definitive primary treatment
Patient judged to be inoperable or at high surgical risk by a board qualified thoracic cancer surgeon who has evaluated the subject within the prior 12 weeks, or the patient's case has been discussed at a multidisciplinary tumor board with a thoracic cancer surgeon in attendance, or a patient who refuses surgery or declines to be evaluated for surgery.
Able to give informed consent
Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2
Men or women of child bearing potential must agree to use an acceptable method of birth control (hormonal or barrier method of birth control; abstinence) to avoid pregnancy for at least 90 days after last study treatment (radiation or fresolimumab)

Exclusion criteria

Exclusion Criteria:

Significant anemia (hemoglobin below 9.0 g/dL) or neutropenia (absolute neutrophil count [ANC] \< 1000/mm\^3)
Prior history of multifocal adenocarcinoma in situ (ie, classic or pure bronchioloalveolar carcinoma)
Prior history of keratoacanthoma (well differentiated squamous cell skin cancer variant, often centrally ulcerated); history of basal cell cancer is allowed
Pre malignant skin lesion(s) noted on prescreening skin exam, except for actinic (solar) keratosis
Prior radiotherapy overlapping with high dose region of planned SABR course
Prior history of head and neck; oral; or bladder cancer
Prior receipt of systemic treatment (chemotherapy, targeted therapy, or immunotherapy) for the lesion under consideration of treatment
Uncontrolled, inter current or recent illness that in the investigator's opinion precludes participation in the study, including those undergoing therapy for a separate invasive malignancy
Contraindication to receiving radiotherapy
Known allergy to components of fresolimumab
Pregnant or breastfeeding. All women of child bearing potential (last menstrual period within the previous 12 months and not surgically sterile) will be tested for pregnancy at pre entry.

Study design

Phase: Phase 1 / Phase 2
Primary purpose: Treatment
Allocation: Non-randomized
Intervention model: Single group
Masking: None (open label)
Enrollment: 28 participants (actual)

Study arms

Experimental
(Phase 1) Fresolimumab 3 mg/kg
Patients receive fresolimumab 3 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.
Biological: Fresolimumab · Radiation: Stereotactic Body Radiation Therapy
Experimental
(Phase 1) Fresolimumab 1 mg/kg
Patients receive fresolimumab 1 mg/kg IV on days 1, 15, and 36 and undergo SABR in 4 fractions between days 8 and 12.
Biological: Fresolimumab · Radiation: Stereotactic Body Radiation Therapy
Experimental
(Phase 2) Fresolimumab
Fresolimumab will be administered IV at the dose selected in the preceding Phase 1 on Days 1, 15 and 36 and SABR will be administered in 4 fractions between Days 8 and 12.
Biological: Fresolimumab · Radiation: Stereotactic Body Radiation Therapy

Interventions

BiologicalFresolimumab
Given IV
Also known as: Anti-TGF-Beta Monoclonal Antibody GC1008, GC1008, Human Anti-TGF-Beta Monoclonal Antibody GC1008, Immunoglobulin G4, anti-(transforming growth factor beta) (human monoclonal GC-1008 heavy chain), disulfide with human monoclonal GC-1008 light chain, Dimer
RadiationStereotactic Body Radiation Therapy
Undergo SABR
Also known as: SBRT

What researchers measure

Primary outcomes

Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I)
DLT is defined as CTCAE grade 3 or higher radiation pneumonitis or bronchopulmonary hemorrhage.
Time frame: Up to 30 days
Number of Participants With Late Radiation Induced Fibrosis
Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is primary in phase 2 patients.
Time frame: 12 months

Secondary outcomes

Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients)
Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is secondary for phase 1 patients.
Time frame: 12 months

Results

Posted Mar 27, 2024

Participant flow

Phase 1

Participant flow — Phase 1
Milestone	(Phase 1) Fresolimumab 3 mg/kg	(Phase 1) Fresolimumab 1 mg/kg	(Phase 2) Fresolimumab
Started	5	0	0
Received treatment	5	0	0
Completed radiation	4	0	0
Completed freso treatments	4	0	0
Completed 12-month follow-up visit	5	0	0
Completed	4	0	0
Not completed	1	0	0

Phase 2

Participant flow — Phase 2
Milestone	(Phase 1) Fresolimumab 3 mg/kg	(Phase 1) Fresolimumab 1 mg/kg	(Phase 2) Fresolimumab
Started	0	0	19
Received treatment	0	0	18
Completed radiation	0	0	17
Completed freso treatments	0	0	13
Completed 12-month follow-up visit	0	0	13
Completed	0	0	12
Not completed	0	0	7

Outcome measures

PrimaryNumber of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I)

DLT is defined as CTCAE grade 3 or higher radiation pneumonitis or bronchopulmonary hemorrhage.

Time frame:: Up to 30 days
Reported as:: Count of participants · Participants

Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I)
Participants	(Phase 1) Fresolimumab 3 mg/kg
Number of Participants Experiencing Dose Limiting Toxicities (DLTs) of Fresolimumab When Combined With SABR (Phase I)	0

PrimaryNumber of Participants With Late Radiation Induced Fibrosis

Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is primary in phase 2 patients.

Time frame:: 12 months
Reported as:: Count of participants · Participants

Number of Participants With Late Radiation Induced Fibrosis
Participants	(Phase 2) Fresolimumab
Number of Participants With Late Radiation Induced Fibrosis	5

SecondaryNumber of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients)

Presence of radiation induced pulmonary fibrosis is defined as presence of a moderate-to-severe level of fibrosis. This outcome is secondary for phase 1 patients.

Time frame:: 12 months
Reported as:: Count of participants · Participants

Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients)
Participants	(Phase 1) Fresolimumab 3 mg/kg
Number of Participants With Late Radiation Induced Fibrosis (Phase 1 Patients)	1

Adverse events

Collected over 12 months. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
(Phase 1) Fresolimumab 3 mg/kg	4/5 (80%)	0/5 (0%)	5/5 (100%)
(Phase 2) Fresolimumab	5/19 (26.3%)	6/19 (31.6%)	15/19 (78.9%)

Most frequent serious events

Most frequent serious events
Event	(Phase 1) Fresolimumab 3 mg/kg	(Phase 2) Fresolimumab
dyspneaRespiratory, thoracic and mediastinal disorders	0/5	3/19
anemiaBlood and lymphatic system disorders	0/5	2/19
av blockCardiac disorders	0/5	1/19
upper gastrointestinal hemorrhageGastrointestinal disorders	0/5	1/19
lung infectionInfections and infestations	0/5	1/19
sepsisInfections and infestations	0/5	1/19
dehydrationMetabolism and nutrition disorders	0/5	1/19
encephalopathyNervous system disorders	0/5	1/19
mental changes statusNervous system disorders	0/5	1/19
respiratory failureRespiratory, thoracic and mediastinal disorders	0/5	1/19

Most frequent other events

Showing 10 of 43

Most frequent other events
Event	(Phase 1) Fresolimumab 3 mg/kg	(Phase 2) Fresolimumab
musculoskeletal painMusculoskeletal and connective tissue disorders	0/5	8/19
nauseaGastrointestinal disorders	2/5	1/19
fatigueGeneral disorders	2/5	6/19
coughRespiratory, thoracic and mediastinal disorders	1/5	7/19
anemiaBlood and lymphatic system disorders	0/5	5/19
headacheNervous system disorders	0/5	4/19
dyspneaRespiratory, thoracic and mediastinal disorders	1/5	4/19
abdominal painGastrointestinal disorders	1/5	1/19
anorexiaMetabolism and nutrition disorders	1/5	2/19
pneumonitisRespiratory, thoracic and mediastinal disorders	1/5	2/19

Baseline characteristics

Age, Customized
Age, Customized(Participants)	(Phase 1) Fresolimumab 3 mg/kg	(Phase 2) Fresolimumab	Total
50-59 years	0	1	1
60-69 years	2	4	6
70-79 years	3	9	12
80-89 years	0	5	5

Sex: Female, Male
Sex: Female, Male(Participants)	(Phase 1) Fresolimumab 3 mg/kg	(Phase 2) Fresolimumab	Total
Female	3	8	11
Male	2	11	13

Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)	(Phase 1) Fresolimumab 3 mg/kg	(Phase 2) Fresolimumab	Total
Hispanic or Latino	0	0	0
Not Hispanic or Latino	5	19	24
Unknown or Not Reported	0	0	0

Race (NIH/OMB)
Race (NIH/OMB)(Participants)	(Phase 1) Fresolimumab 3 mg/kg	(Phase 2) Fresolimumab	Total
American Indian or Alaska Native	0	0	0
Asian	0	2	2
Native Hawaiian or Other Pacific Islander	0	1	1
Black or African American	0	2	2
White	5	14	19
More than one race	0	0	0
Unknown or Not Reported	0	0	0

Region of Enrollment
Region of Enrollment(Participants)	(Phase 1) Fresolimumab 3 mg/kg	(Phase 2) Fresolimumab	Total
United States	5	19	24

Study locations

1 site

Stanford University, School of Medicine
Palo Alto, California 94304, United States

References and documents

Study documents

Protocol and statistical analysis plan · Jun 30, 2022

Documents are hosted by the registry — open the source record to download them.

Updates

Tracking since Sep 25, 2026

No changes since tracking began. The registry record was last updated on Mar 27, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT02581787
Lead sponsor: Maximilian Diehn
Collaborators: Varian Medical Systems
Responsible party: Maximilian Diehn (Assistant Professor of Radiation Oncology, Stanford University) — Sponsor-investigator
First posted: Oct 21, 2015
Start date: Aug 2016
Primary completion: Mar 2, 2023
Completion: Mar 2, 2023
Results posted: Mar 27, 2024
Last update: Mar 27, 2024

Study contacts

Maximilian Diehn

principal investigator · Stanford Cancer Institute

Oversight

Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No

View the source record on ClinicalTrials.gov ↗

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